Anti il-36r antibodies

Abstract

The present invention relates to anti-IL-36R binding compounds, in particular new anti-IL-36R antibodies and therapeutic and diagnostic methods and compositions for using the same.

1 . An anti-IL-36R antibody or antigen-binding fragment thereof which specifically binds to Interleukin-36 Receptor (IL36R) comprising:
 (i) a light chain immunoglobulin variable region comprising the CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 77; and a heavy chain immunoglobulin variable region comprising the CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 87; or   (ii) a light chain immunoglobulin variable region comprising the CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 77; and a heavy chain immunoglobulin variable region comprising the CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 88; or   (iii) a light chain immunoglobulin variable region comprising the CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 77; and a heavy chain immunoglobulin variable region comprising the CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 89; or   (iv) a light chain immunoglobulin variable region comprising the CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 80; and a heavy chain immunoglobulin variable region comprising the CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 87; or   (v) a light chain immunoglobulin variable region comprising the CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 80; and a heavy chain immunoglobulin variable region comprising the CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 88; or   (vi) a light chain immunoglobulin variable region comprising the CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 80; and a heavy chain immunoglobulin variable region comprising the CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 89; or   (vii) a light chain immunoglobulin variable region comprising the CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 85; and a heavy chain immunoglobulin variable region comprising the CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 100; or   (viii) a light chain immunoglobulin variable region comprising the CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 85; and a heavy chain immunoglobulin variable region comprising the CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO:101; or   (ix) a light chain immunoglobulin variable region comprising the CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 86; and a heavy chain immunoglobulin variable region comprising the CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 100; or   (x) a light chain immunoglobulin variable region comprising the CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO: 86; and a heavy chain immunoglobulin variable region comprising the CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region that comprises the amino acid sequence set forth in SEQ ID NO:101.   
     
     
         2 . An anti-IL-36R antibody according to  claim 1 , wherein the antibody comprises:
 (i) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 77, and at least 90% identical to SEQ ID NO:115; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 87 and at least 90% identical to SEQ ID NO: 125; or   (ii) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 77 and at least 90% identical to SEQ ID NO:115; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 88 and at least 90% identical to SEQ ID NO: 126; or   (iii) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 77 and at least 90% identical to SEQ ID NO:115; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 89 and at least 90% identical to SEQ ID NO:127; or   (iv) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 80 and at least 90% identical to SEQ ID NO:118; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 87 and at least 90% identical to SEQ ID NO: 125; or   (v) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 80 and at least 90% identical to SEQ ID NO:118; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 88 and at least 90% identical to SEQ ID NO: 126; or   (vi) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 80 and at least 90% identical to SEQ ID NO:118; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 89 and at least 90% identical to SEQ ID NO: 127; or   (vii) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 85 and at least 90% identical to SEQ ID NO: 123; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 100 and at least 90% identical to SEQ ID NO: 138; or   (viii) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 85 and at least 90% identical to SEQ ID NO: 123; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 101 and at least 90% identical to SEQ ID NO: 139; or   (ix) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 86 and at least 90% identical to SEQ ID NO: 124; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 100 and at least 90% identical to SEQ ID NO: 138; or   (x) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 86 and at least 90% identical to SEQ ID NO: 124; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 101 and at least 90% identical to SEQ ID NO: 139.   
     
     
         3 . The antibody or antigen-binding fragment thereof of  claim 1  which is produced by a method comprising:
 (i) introducing one or more polynucleotides encoding the heavy and light chain immunoglobulin variable regions of said antibody or antigen-binding fragment thereof into an isolated host cell; 
 (ii) culturing the host cell in a medium under conditions favorable to expression of the polynucleotide; and 
 (iii) optionally, isolating the antibody or antigen-binding fragment thereof from the host cell and/or medium in which the host cell is grown. 
 
     
     
         4 . An anti-IL-36R antibody according to  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 115; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 125. 
     
     
         5 . An anti-IL-36R antibody according to  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 115; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 126. 
     
     
         6 . An anti-IL-36R antibody according to  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 115; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 127. 
     
     
         7 . An anti-IL-36R antibody according to  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 118; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 125. 
     
     
         8 . An anti-IL-36R antibody according to  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 118; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 126. 
     
     
         9 . An anti-IL-36R antibody according to  claim 1 , wherein the antibody thereof comprises a light chain comprising the amino acid sequence of SEQ ID NO: 118; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 127. 
     
     
         10 . An anti-IL-36R antibody according to  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 138. 
     
     
         11 . An anti-IL-36R antibody according to  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139. 
     
     
         12 . An anti-IL-36R antibody according to  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 138. 
     
     
         13 . The anti-IL-36R antibody or antigen-binding fragment of  claim 1 , wherein said antibody or antigen-binding fragment thereof binds to human IL-36R at a K D  equal to or <0.1 nM. 
     
     
         14 . The anti-IL-36R antibody or antigen-binding fragment of  claim 1 , wherein said antibody or antigen-binding fragment thereof inhibits IL-36R mediated signaling elicited by each of IL-36a, IL-36P and IL36γ, wherein inhibition of signaling mediated by the IL-36 receptors are determined in disease-relevant cell lines and primary cells relative to a control in the absence of said antigen or antigen binding fragment. 
     
     
         15 . The anti-IL-36R antibody or antigen-binding fragment of  claim 1 , wherein said antibody or antigen-binding fragment thereof does not bind to human IL-1 R1. 
     
     
         16 . The anti-IL-36R antibody or antigen-binding fragment of  claim 1 , wherein the said antibody or antigen-binding fragment thereof comprises a F(ab′)2 fragment of a humanized anti-IL-36R antibody comprising a light chain sequence of any of SEQ ID NO: 115 or 118 in combination with a heavy chain sequence of SEQ ID NO: 125, 126 or 127. 
     
     
         17 . The anti-IL-36R antibody or antigen-binding fragment of  claim 1 , wherein the said antibody or antigen-binding fragment thereof comprises a F(ab′)2 fragment of a humanized anti-IL-36R antibody comprising a light chain sequence of any of SEQ ID NO: 123 or 124 in combination with a heavy chain sequence of SEQ ID NO: 138 or 139. 
     
     
         18 . A pharmaceutical composition comprising an antibody or antigen-binding fragment according to  claim 1  and a pharmaceutically acceptable carrier.